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Implant-related infections are serious complications after bone surgery and can compromise the intended functions of artificial implants, leading to surgical failure and even amputation in severe cases. Various strategies have been proposed to endow bone implants with the desirable antibacterial properties, but unfortunately, most of them inevitably suffer from some side effects detrimental to normal tissues. In this study, a multifunctional bone implant is designed to work in conjunction with sequential photothermal mediation, which can deliver antibacterial therapy (<50 °C) in the early stage and foster bone regeneration (40-42 °C) subsequently. Black phosphorus nanosheets (BPs) are coordinated with zinc sulfonate ligand (ZnL 2 ), and the ZnL 2 -BPs are integrated into the surface of a hydroxylapatite (HA) scaffold to produce ZnL 2 -BPs@HAP. In this design, BPs produce the photothermal effects and ZnL 2 increases the thermal sensitivity of peri-implant bacteria by inducing envelope stress. The biosafety of the antibacterial photothermal treatment is improved due to the mild temperature, and furthermore, gradual release of Zn 2+ and PO 4 from the scaffold facilitates osteogenesis in the subsequent stage of bone healing. This strategy not only broadens the biomedical applications of photothermal treatment but also provides insights into the design of multifunctional biomaterials in other fields.3- from the scaffold facilitates osteogenesis in the subsequent stage of bone healing. This strategy not only broadens the biomedical applications of photothermal treatment but also provides insights into the design of multifunctional biomaterials in other fields.

Various bifunctional scaffolds have recently been developed to address the reconstruction of tumor-initiated bone defects. Such scaffolds are usually composed of a near-infrared (NIR) photothermal conversion agent and a conventional bone scaffold for photothermal therapy (PTT) and long-term bone regeneration. However, the reported photothermal conversion agents are mainly restricted to the first biological window (NIR-I) with intrinsic poor tissue penetration depth. Also, most of these agents are non-bioactive materials, which induced potential systemic side toxicity after implantation. Herein, a NIR-II photothermal conversion agent (Wesselsite [SrCuSi 4 O 10 ] nanosheets, SC NSs) with tremendous osteogenic and angiogenic bioactivity, is rationally integrated with polycaprolactone (PCL) via 3D printing. The as-designed 3D composite scaffolds not only trigger osteosarcoma ablation through NIR-II light generated extensive hyperthermia, but also promote in vitro cellular proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) and human umbilical vein endothelial cells (HUVECs), respectively, and the ultimate enhancement of vascularized bone regeneration in vivo owing to the controlled and sustained release of bioactive ions (Sr, Cu, and Si). The authors' study provides a new avenue to prepare multifunctional bone scaffolds based on therapeutic bioceramics for repairing tumor-induced bone defects., (© 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.)

The hierarchical microstructure, surface and interface of biomaterials are important factors influencing their bioactivity. Porous bioceramic scaffolds have been widely used for bone tissue engineering by optimizing their chemical composition and large-pore structure. However, the surface and interface of struts in bioceramic scaffolds are often ignored. The aim of this study is to incorporate hierarchical pores and bioactive components into the bioceramic scaffolds by constructing nanopores and bioactive elements on the struts of scaffolds and further improve their bone-forming activity. Mesoporous bioactive glass (MBG) modified β-tricalcium phosphate (MBG-β-TCP) scaffolds with a hierarchical pore structure and a functional strut surface (∼100 nm of MBG nanolayer) were successfully prepared via 3D printing and spin coating. The compressive strength and apatite-mineralization ability of MBG-β-TCP scaffolds were significantly enhanced as compared to β-TCP scaffolds without the MBG nanolayer. The attachment, viability, alkaline phosphatase (ALP) activity, osteogenic gene expression (Runx2, BMP2, OPN and Col I) and protein expression (OPN, Col I, VEGF, HIF-1α) of rabbit bone marrow stromal cells (rBMSCs) as well as the attachment, viability and angiogenic gene expression (VEGF and HIF-1α) of human umbilical vein endothelial cells (HUVECs) in MBG-β-TCP scaffolds were significantly upregulated compared with conventional bioactive glass (BG)-modified β-TCP (BG-β-TCP) and pure β-TCP scaffolds. Furthermore, MBG-β-TCP scaffolds significantly enhanced the formation of new bone in vivo as compared to BG-β-TCP and β-TCP scaffolds. The results suggest that application of the MBG nanolayer to modify 3D-printed bioceramic scaffolds offers a new strategy to construct hierarchically porous scaffolds with significantly improved physicochemical and biological properties, such as mechanical properties, osteogenesis, angiogenesis and protein expression for bone tissue engineering applications, in which the incorporation of nanostructures and bioactive components into the scaffold struts synergistically play a key role in the improved bone formation.

Polymer biomaterials have been widely used for bone replacement/regeneration because of their unique mechanical properties and workability. Their inherent low bioactivity makes them lack osseointegration with host bone tissue. For this reason, bioactive inorganic particles have been always incorporated into the matrix of polymers to improve their bioactivity. However, mixing inorganic particles with polymers always results in inhomogeneity of particle distribution in polymer matrix with limited bioactivity. This study sets out to apply the pulsed laser deposition (PLD) technique to prepare uniform akermanite (Ca2MgSi2O7, AKT) glass nanocoatings on the surface of two polymers (non-degradable polysulfone (PSU) and degradable polylactic acid (PDLLA)) in order to improve their surface osteogenic and angiogenic activity. The results show that a uniform nanolayer composed of amorphous AKT particles (∼30 nm) of thickness 130 nm forms on the surface of both PSU and PDLLA films with the PLD technique. The prepared AKT-PSU and AKT-PDLLA films significantly improved the surface roughness, hydrophilicity, hardness and apatite mineralization, compared with pure PSU and PDLLA, respectively. The prepared AKT nanocoatings distinctively enhance the alkaline phosphate (ALP) activity and bone-related gene expression (ALP, OCN, OPN and Col I) of bone-forming cells on both PSU and PDLLA films. Furthermore, AKT nanocoatings on two polymers improve the attachment, proliferation, VEGF secretion and expression of proangiogenic factors and their receptors of human umbilical vein endothelial cells (HUVEC). The results suggest that PLD-prepared bioceramic nanocoatings are very useful for enhancing the physicochemical, osteogenic and angiogenic properties of both degradable and non-degradable polymers for application in bone replacement/regeneration., (Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) and osteogenic revulsants alone or in combination at different time points and in different dosages on proliferation and osteogenesis of bone marrow stromal cells (BMSCs) in SD rats were investigated. Rat BMSCs were cultured in vitro and induced by rhBMP-2 in different dosages (10, 50, 100 and 200 mug/L) alone or in combination with osteogenic revulsants. MTT colorimetric assay was used to evaluate The proliferation, activity of alkaline phosphoric (ALP) and osteocalcin were measured at 3rd, 6th, 9th, 12th day respectively. The results showed that rhBMP-2 and osteogenic revulsants could promote the differentiation of BMSCs towards osteoblast phenotype. The proliferation of BMSCs could be enhanced by rhBMP-2 in a dose-dependent manner. The expression of osteoblast phenotype was significantly higher by using both of them than by using them alone, which was verified by the activity of ALP and osteocalcin. It was suggested that the combined use of rhBMP-2 and osteogenic revulsants could promote the proliferation and simultaneously induce and maintain the expression of osteoblast phenotype of BMSCs in rats.

[Display omitted] • Scaffolds with DOX-gelatin/SrCuSi 4 O 10 -β-TCP core/shell filaments were fabricated. • SrCuSi 4 O 10 endowed the scaffolds with PTT at NIR-II window. • NIR-II irradiation also triggered the on-demand DOX release, achieving accurate chemotherapy. • The produced channels and released bioactive ions enhanced the vascularized bone regeneration. The treatment of bone defect caused by osteosarcoma remains an intractable problem. Scaffolds with multi-functions are the potential candidates to kill recurrent tumor and to repair the bone defects after tumorectomy. However, most of these scaffolds employed photothermal therapy using near‐infrared laser in the first biological window (NIR‐I) with intrinsic poor tissue penetration depth. Some scaffolds loading drugs for chemotherapy generally lack the accurate control of on-demand drugs release to reduce the side effects and enhance the therapeutic efficacy. Herein, 3D printed gelatin/bioceramics core/shell scaffolds were developed with doxorubicin (DOX) loaded gelatin as the core part and SrCuSi 4 O 10 (SC) nanosheets/beta-tricalcium phosphate (β-TCP) as the shell part of the printed filaments. SC nanosheets endowed the scaffolds with photothermal therapy under NIR-II laser irradiation. Simultaneously, the generated extensive hyperthermia could induce the gel-sol transition of the gelatin in the core part of the filaments, which subsequently triggered the on-demand DOX release from the loosened gelatin achieving chemo-photothermal therapy. The in vitro and in vivo data demonstrated that chemo-photothermal therapy showed a synergetic effect on anti-tumor. Additionally, the degradation/release of gelatin from the filaments resulted in the hollow channels in the scaffold, which provided clear architectural cues for promoting the ingrowth of bone tissues. Meanwhile, the degradation of the SC nanosheets contributed to the sustained release of bioactive ions (Sr, Cu and Si), which further enhanced vascularized bone regeneration. All these results indicated that the 3D printed DOX loaded gelatin-TCP/SC scaffolds had a great potential application for the treatment of bone defects caused by osteosarcoma in effective killing cancer cells and repairing tumor-induced bone defects. [ABSTRACT FROM AUTHOR]